Simple approach to assess potentiated drug combinations in clinical trials: studies with pirenzepine plus H2-receptor antagonists

Abstract

A simple approach to prove or disprove potentiation is described, which is based on the comparison of observed effects of reversibly acting drugs A plus B with effects of independently acting drugs in combination, since the latter already represent a special type of overadditive drug combination, i.e., potentiation. As an example, secretory studies in man using combinations of the antimuscarinic drug pirenzepine and the H2-receptor antagonists cimetidine or ranitidine were reevaluated. In these studies combined antisecretory effects were found which not only correspond to those of independently acting (i.e., functional) synergists, but even significantly exceed them. Pirenzepine caused 60 +/- 4.0%, and cimetidine 61 +/- 4.6% inhibition of peptone-stimulated acid secretion. In combination the effect amounted to 90 +/- 0.8% (n = 8) which is more pronounced than the calculated effect of functional synergists (83 +/- 3.1%). Similar results were obtained with pirenzepine plus ranitidine. Hence, a true interaction between antimuscarinic and H2-receptor antagonizing drugs to suppress gastric acid secretion can be assumed.